We have achieved long-term, immunologically specific suppression (enhancement) of renal allografts in the rat by treating the recipient with donor antigen and antidonor allo-antibody. Recent evidence suggests that production of anti-idiotypic antibody against idiotypic determinants in the enhancing serum may be important for the induction and perhaps maintenance of enhanced kidney grafts. The objectives of the proposed study are to define the role of anti-idiotypic antibody in enhancement of rat renal allografts; explore the possibility of inducing anti-idiotypic antibody in a rabbit kidney transplant model; and to attempt to enhance renal allografts in outbred rabbits by treatment with donor antigen and antidonor antibody or its F(ab')2 fragments. Current methods of suppressing allograft rejection in man employ a variety of agents that are all immunologically non-specific; they suppress the response to many antigens in addition to the histocompatibility antigens that are represented on an allograft. Frequently, the price for preventing graft rejection with these agents is increased susceptibility to a spectrum of pathogens. In addition, the drugs may have serious untoward side effects such as leukopenia and gastrointestinal hemorrhage. The eventual goal of our research is to achieve specific suppression of allograft rejection which will be applicable to man.